Background
Diabetes mellitus is a common endocrine disease which is mainly characterized by chronic hyperglycemia, glycolipid metabolism and protein metabolism disorder, and the pathogenesis of diabetes mellitus is mainly due to absolute insufficient insulin secretion and islet resistance. When insulin is insufficient, the serum glucose content is continuously increased and exceeds the reabsorption capability of the kidney, so that a large amount of glucose is excreted along with urine, osmotic diuresis is caused, the body is dehydrated, brain cells lose water, brain dysfunction can be caused to be coma, and because a diabetic patient has sugar utilization disorder, energy is generated by decomposing fat, and the generation of ketone bodies is increased along with the fat decomposition, so that diabetic ketoacidosis is caused. Research shows that oxidative stress is closely related to the formation of diabetes, and excessive free radical generation by oxidative stress can cause the functional damage of islet beta cells, insufficient insulin secretion and peripheral insulin resistance, induce the formation of diabetes, and cause various complications such as diabetic neuropathy, diabetic retinopathy, diabetic cardiovascular and cerebrovascular diseases and the like.
Most of the hypoglycemic drugs commonly used in clinical practice are chemically synthesized drugs (such as alpha-glycosidase inhibitors). The toxic effects of enteroglycosidases through inhibition of hyperglycemia are associated not only with prolonged elevated blood glucose, but also with the relative levels of postprandial elevated blood glucose. After entering the small intestine, the polysaccharides in the food are degraded into some oligosaccharides and disaccharides by amylase, and then decomposed into monosaccharides by alpha-glucosidase at the brush border of the small intestine to be absorbed into the blood. Competitive inhibition of small intestinal glucosidase therefore reduces postprandial hyperglycemia levels. However, these drugs can cause serious adverse reactions when taken for a long time, such as: nausea, vomiting, abdominal discomfort, and the like, as well as leukopenia, ketonuria, lactic acidosis, and the like, have limited applications. The research and development of natural antidiabetic drugs with high efficiency, low toxicity and low price for reducing blood sugar to relieve diabetic complications is a problem to be solved urgently in clinic. Therefore, the search of high-efficiency hypoglycemic drugs from plants becomes one of the key points of the research of antidiabetic drugs at home and abroad.
CN106924479A discloses a traditional Chinese medicine composition for reducing blood sugar, which comprises the following traditional Chinese medicines in parts by mass: 16-20 parts of kudzuvine root, 16-20 parts of astragalus, 16-20 parts of hairyvein agrimony, 15-19 parts of mulberry leaf, 15-19 parts of tuber fleeceflower root, 15-19 parts of pine pollen, 14-18 parts of medlar, 14-18 parts of Chinese magnoliavine fruit, 14-18 parts of glossy privet fruit, 12-14 parts of cortex moutan, 12-14 parts of szechwan chinaberry fruit, 12-14 parts of tuber fleeceflower root, 10-12 parts of liquorice, 10-12 parts of green plum blossom, 8-10 parts of spina date seed, 5-7 parts of momordica grosvenori, 5-7 parts of honeysuckle, 3-5 parts of cyclocarya paliurus leaves, 1-3 parts of Chinese yam and 1-3 parts of szechuan lovage rhizome. The traditional Chinese medicine composition for reducing blood sugar is natural and safe, and can reduce the blood sugar level of a diabetic patient and improve the symptoms of the diabetic patient.
CN108272984A discloses a medicine for reducing blood sugar, which comprises the following raw materials in parts by weight: 16-22 parts of cyclocarya paliurus, 6-10 parts of kudzu root, 3-5 parts of phaseolus calcaratus, 5-8 parts of radix rehmanniae recen, 4-6 parts of asparagus, 10-15 parts of cucumber, 8-14 parts of bitter gourd, 1.8-4 parts of grandma and 4-8 parts of coptis chinensis.
According to the traditional Chinese medicine, the 'turbid glycolipid metabolic disease' is a disease which takes emotional disorder, improper diet, insufficient innate endowment or senile asthenia as main causes, liver dysfunction as a core pathogenesis, damp, phlegm, stasis, heat and toxin as main pathological products, and depression or irritability, obesity or emaciation, heavy head and body, bitter taste and sticky mouth, chest and hypochondrium swelling or pain, fatigue and hypodynamia, dry throat and dry mouth and other main clinical manifestations. Clinically, the "fever" and the "turbidity" are often seen mutually, and are mutually interwoven and mutually influenced, so the combined use of the turbidity is taken as a disease covering the pathological changes of hyperglycemia, hyperlipidemia, atheromatous plaque, vascular injury and the like caused by the disorder of the glycometabolism and the lipotropia and the multi-organ affected characteristics thereof.
The invention starts the spleen pivot qi movement to go up and down and come in and go out by regulating the liver function, and regulates the metabolism of essence, blood and body fluid to dispel damp phlegm and turbid blood stasis, thereby correcting the in vivo glycolipid metabolic disturbance and realizing the purpose of comprehensively regulating and controlling the glycolipid metabolic disease (fever).
Disclosure of Invention
In view of the above, the invention provides a traditional Chinese medicine composition and an application thereof in preparing a hypoglycemic medicament.
In order to achieve the purpose, the invention adopts the following technical scheme:
a Chinese medicinal composition comprises cyclocarya paliurus, radix Puerariae and fructus Citri Sarcodactylis.
Preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 5-20 parts of cyclocarya paliurus, 10-30 parts of kudzu root and 8-36 parts of fingered citron.
Preferably, the traditional Chinese medicine composition further comprises cordyceps militaris.
Further preferably, the cordyceps militaris is 5-15 parts by weight.
The kudzu root in the invention can also be kudzu, the technical effects of the invention can be realized by the technical schemes, and in some preferred embodiments, the achieved technical effects are superior to other schemes.
For example:
the mass ratio of cyclocarya paliurus to radix puerariae is 1: 1, wherein the preferable traditional Chinese medicine composition comprises the following specific components in parts by weight: 10 parts of cyclocarya paliurus, 10 parts of kudzu root and 10 parts of fingered citron.
The mass ratio of cyclocarya paliurus, the radix puerariae and the cordyceps militaris is 7: 7: 6, one of the preferable traditional Chinese medicine compositions comprises the following specific components in parts by weight: 14 parts of cyclocarya paliurus, 14 parts of kudzu root, 24 parts of fingered citron and 12 parts of cordyceps militaris.
The invention also provides a traditional Chinese medicine extract which is extracted from the traditional Chinese medicine composition.
Preferably, the extraction is: the extraction method comprises at least one of water decoction, soaking, percolation, modified gelatin, reflux, solvent extraction, steam distillation, sublimation, supercritical fluid extraction, membrane separation, micronization, flocculation separation of Chinese medicinal materials, semi-bionic extraction, ultrasonic extraction, cyclone extraction, pressurized countercurrent extraction, enzyme method, macroporous resin adsorption, ultrafiltration, and molecular distillation.
The invention provides a method for preparing the traditional Chinese medicine extract, which comprises the following steps: extracting the raw materials according to the formula amount with water, combining the filtrates, concentrating under reduced pressure to obtain dry extract, and pulverizing to obtain the traditional Chinese medicine extract.
The invention also provides a medicament which comprises the traditional Chinese medicine composition, the traditional Chinese medicine extract or the traditional Chinese medicine extract prepared by the preparation method.
The invention also provides the application of the traditional Chinese medicine composition, the traditional Chinese medicine extract or the traditional Chinese medicine extract prepared by the preparation method in preparing medicines and/or health-care products for reducing blood sugar.
The invention has the beneficial effects that: (1) compared with the dialectical theory of treating diabetes from the spleen in the prior art, the traditional Chinese medicine composition disclosed by the invention selects cyclocarya paliurus, the root of kudzu vine and the fingered citron as main raw materials, starts the spleen pivot qi movement to go up and down and come in and out by regulating the function of the liver, and regulates the metabolism of essence, blood and body fluid to dispel damp phlegm and turbid blood stasis, so that the metabolic disorder of glycolipid in vivo is corrected, and the purpose of comprehensively regulating and controlling the glycolipid metabolism (turbid pathogen) is realized.
(2) The invention exerts better effects of reducing blood sugar and repairing insulin functions through the synergistic effect of the three raw materials, has no damage to liver and kidney in the taking process, has certain effect of protecting liver, has the advantages of safety and no stimulation, and can be used for a long time.
(3) When a specific amount of cordyceps militaris is added, a synergistic effect can be further exerted, and the islet cell recovery level is improved.
Detailed Description
The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.
Before the present embodiments are further described, it is to be understood that the scope of the invention is not limited to the particular embodiments described below; it is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention.
When numerical ranges are given in the examples, it is understood that both endpoints of each of the numerical ranges and any value therebetween can be selected unless the invention otherwise indicated. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
The sources of the raw materials used in the present invention are not limited, and the raw materials used in the present invention are all those commonly available in the art unless otherwise specified. The cyclocarya paliurus adopted by the implementation is cyclocarya paliurus leaves.
Basic embodiment
A traditional Chinese medicine composition comprises the following raw materials: cyclocarya paliurus, radix puerariae and fingered citron.
Preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 5-20 parts of cyclocarya paliurus, 10-30 parts of kudzu root and 8-36 parts of fingered citron.
Preferably, the traditional Chinese medicine composition further comprises cordyceps militaris.
Further preferably, the cordyceps militaris is 5-15 parts by weight.
The technical effects of the invention can be realized by the technical schemes, and in some preferred embodiments, the achieved technical effects are superior to other schemes.
For example:
the mass ratio of cyclocarya paliurus to radix puerariae is 1: 1, wherein the preferable traditional Chinese medicine composition comprises the following specific components in parts by weight: 10 parts of cyclocarya paliurus, 10 parts of kudzu root and 10 parts of fingered citron.
The mass ratio of cyclocarya paliurus, the radix puerariae and the cordyceps militaris is 7: 7: 6, one of the preferable traditional Chinese medicine compositions comprises the following specific components in parts by weight: 14 parts of cyclocarya paliurus, 14 parts of kudzu root, 24 parts of fingered citron and 12 parts of cordyceps militaris.
Examples and comparative examples A Chinese medicinal composition and method for preparing the same
The raw materials and the amounts (parts by weight) of the Chinese medicinal compositions described in examples 1 to 6 and comparative examples 1 to 2 are shown in Table 1.
TABLE 1
Remarking: in the table, "+" represents 12 parts of mulberry leaves and "-" represents no addition.
The preparation method comprises the following steps: taking raw materials according to the prescription amount, mixing and extracting for 2 times, adding 10 times of water (weight of the prescription amount) for the first time, and extracting for 2 hours; filtering, adding 8 times of water (formula weight amount) into the residue, extracting for 1 hr, filtering, mixing filtrates, concentrating under reduced pressure to obtain dry extract, and pulverizing.
Evaluation of efficacy
1 materials of the experiment
The Chinese medicinal compositions prepared in examples 1-6 and comparative examples 1-2.
2 laboratory animals
Experimental animals 4 weeks old, male, healthy C57BL/6J mice, weighing 18-25g, were obtained.
3 Main Equipment, Instrument and consumables
Blood glucose meters (roche); glucose kit (Glu, shanghai nabobism pharmaceutical limited); triglyceride reagent kit (TG, Nanjing institute of bioengineering); a total cholesterol kit (TC, Nanjing institute of bioengineering); high density lipoprotein kit (HDL-C, Nanjing institute of bioengineering); low density lipoprotein kit (LDL-C, Nanjing institute of bioengineering); free fatty acid kit (NEFA, Nanjing institute of bioengineering); mouse Insulin (INS) ELISA kit (brilliant); streptozotocin (STZ, Sigma, usa); citric acid and sodium citrate (guangzhou ruishu biotechnology limited); metformin (shanghai shigui pharmaceutical ltd, midea); glucose (Tianjin Jianyun chemical Co., Ltd.); absolute ethanol (Tianjin Chengyuan chemical reagent, Inc.); d101 macroporous adsorption resin (Dongpo chemical Co., Ltd.).
4 Experimental methods
4.1 random grouping
One week after acclimation feeding, all mice were randomly assigned to the following 2 groups according to body weight by the random number table method: blank control group 10, T2DM group 100. After the T2DM group molding was successful, the following 10 groups were randomly assigned according to blood glucose levels: model group (10), examples 1-6 groups (10 each), comparative examples 1-2 groups (10 each), and positive drug group (10). Mice in the placebo group and High Fat Diet (HFD) fed (60% cholesterol) T2DM group were fed with normal diet.
4.2 Molding method and pharmaceutical intervention
Molding a mouse, after fasting for 12 hours, dissolving the STZ in a citric acid buffer solution (PH4.2) with the concentration of 0.1mmol/L according to the daily dosage of 40mg/kg of body weight, and performing intraperitoneal injection on the mouse; the blank group was injected 1ml/100g of citrate buffer 1 time daily for 4 consecutive days. Blood glucose was measured 72 hours after molding. After the blood sugar rises and stabilizes for 2 weeks, the mice with the concentration more than or equal to 11.1mmol/L are successfully modeled. After 2 weeks, randomly selecting 3 rats for liver pathological observation, wherein liver steatosis occurs to a certain extent, a large amount of lipid drop vacuoles appear in cytoplasm, and measuring Fasting Blood Glucose (FBG) of the rats for more than 2 times is more than or equal to 11.1mmol/L, which indicates that T2DM molding is successful.
According to the clinical dose combination preliminary experiment, the administration dose of the example group and the comparative example group was set as: 1.2g crude drug/kg, the administration mode is intragastric; metformin tablet 250mg/kg (formulated as 100g/L aqueous solution) was administered by gavage at 1mL/100g/d for 12 weeks.
5 index measuring method
5.1 Oral Glucose Tolerance Test (OGTT) test
The feed of the mice is taken out 6 hours in advance, water is normally supplied, and the padding is replaced, because the blood sugar of the mice can be influenced by the feed residues in the padding. The glucose content was measured by gavage at 1.5g/kg and 1ml/100g at 0, 30, 60, 90, 120, 150 min and other time points.
5.2 insulin glucose tolerance test (ITT) test
Fasting is not forbidden for 6 h. Mice were weighed and insulin doses were calculated at 0.5U/kg, insulin being pre-prepared at 0.05U/ml. Blood glucose of each mouse was measured to obtain a blood glucose value at time 0, and then insulin was intraperitoneally injected, and tail blood samples were collected at 15, 30, 60, 90, and 120 minutes after the injection and blood glucose was measured using a glucometer, respectively.
5.3 plasma sample index detection
Mouse FBG was detected at the same time every week. According to the kit specification, the content of HDL-C, LDL-C, NEFA in serum is measured by a direct method, and the TC and TG levels in the serum are measured by a micro-method; plasma INS levels were measured by ELISA and the insulin resistance index (HOMA-IR) was calculated. After the administration, the mice are fasted for 6h, the mice are anesthetized by ether after weighing, the eyeballs are picked up and blood is taken out of a 1.5ml EP tube, the centrifugation is carried out for 10min at 4 ℃ and 3500r/min, and the plasma is separated and frozen at minus 80 ℃ for standby.
Calculating by the formula: insulin resistance index (HOMA-IR) ═ fasting insulin INS × fasting glucose/22.5.
5.4 statistical analysis
Data were analyzed using GraphPad Prism 8.0 software using the two-tailed unpaired Student's t test for comparisons between groups and One-way ANOVA test for more than two groups, with data expressed as Mean ± standard error (Mean ± SEM).
6 results of the experiment
6.1 Effect on mice fasting insulin resistance index, oral glucose tolerance (OGTT) and insulin glucose tolerance
Compared with the blank mice, the fasting insulin resistance index (HOMA-IR) of the model mice has obvious rising change (P is less than 0.001), which indicates that the model building is successful.
Compared with the mice in the model group, the fasting insulin resistance indexes of the mice in the positive drug group, the mice in the example 5 group and the mice in the example 6 group are all reduced, and the significant difference is realized (P is less than 0.05); compared with the model group mice, the fasting insulin resistance indexes of the mice in the positive drug group, the mice in the example 3 group and the mice in the 4 group are all reduced, and the significant difference is shown (P is less than 0.01).
Compared with the blank mice, the area under the OGTT curve of the model mice is obviously increased (P is less than 0.001), which indicates that the model building is successful.
Compared with the mice in the model group, the areas under the OGTT curves of the mice in the positive drug group, the mice in the groups of examples 1-6 and the mice in the comparative example 2 are obviously reduced, and the significant difference is achieved (P is less than 0.05).
Compared with the blank mice, the ITT of the model mice has obvious increase change (P is less than 0.001), which indicates that the modeling is successful.
Compared with the mice in the model group, the ITT of the mice in the positive medicine group and the mice in the example 4 is remarkably reduced (P is less than 0.001); the ITT was significantly reduced in the mice of example 3, 5 and 6 groups compared to the mice of the model group (P < 0.01).
TABLE 1 Effect of Chinese medicinal compositions on mouse OGTT, ITT and HOMA-IR (x + -SEM, n ═ 10)
6.2 Effect on blood indices in T2DM mice
Compared with a blank control group, the Total Cholesterol (TC), Triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) level of the model group mouse is obviously increased (P is less than 0.001), and the high-density lipoprotein cholesterol (HDL-C) level is obviously reduced (P is less than 0.001); free fatty acid (NEFA) levels were significantly elevated (P < 0.05).
The group of positive drugs, examples 1 to 6 and comparative example 2 significantly reduced Total Cholesterol (TC), Triglyceride (TG) and free fatty acid (NEFA) in T2DM mice and increased high density lipoprotein cholesterol (HDL-C) levels, compared to the model group.
Table 2 effect of the Chinese medicinal composition on blood index of T2DM mouse (x ± SEM, n ═ 10)
The results show that the traditional Chinese medicine composition can obviously improve the blood sugar and blood fat metabolism of the STZ-induced diabetic mice, reduce the fasting blood sugar and blood fat levels of the diabetic mice, increase the glucose tolerance and insulin resistance, and partially recover the islet cells to normal level, thereby maintaining the islet function and regulating the glycolipid metabolic disorder.
According to the traditional Chinese medicine composition, cyclocarya paliurus, the root of kudzu vine and the fingered citron are selected as main raw materials, the spleen pivot qi activity is started to go up and down through the function of regulating the liver, the essence, blood and body fluid metabolism is regulated, and the damp phlegm and turbid blood stasis is removed, so that the in-vivo glycolipid metabolic disturbance is corrected, the purpose of comprehensively regulating and controlling the glycolipid metabolic disease (turbid fever) is realized, meanwhile, the traditional Chinese medicine composition has no harm to the liver and the kidney in the taking process, and has a certain liver protection effect. Meanwhile, when a specific amount of cordyceps militaris is added into the composition of cyclocarya paliurus, radix puerariae and fingered citron, the synergistic effect can be further exerted, and the recovery level of islet cells is improved.
The present invention has been further described with reference to specific embodiments, which are only exemplary and do not limit the scope of the present invention. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.